Coronary flow reserve (CFR, calculated as the ratio of hyperemic to rest myocardial blood flow) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. It provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease, diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion. Inflammation is a key mediator of this constellation of abnormalities and affects the entire coronary vasculature. The recently launched Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity for mechanistic investigation of the impact of anti-inflammatory therapy on changes in CFR as a reflection of coronary vascular dysfunction, which may precede clinical outcomes, particularly in high-risk patients. a In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular (LV) deformation and, ultimately, symptoms and prognosis. Accordingly, 2 specific aims are proposed: (1) To test the hypothesis that LDM at a target dose of 15 to 20 mg orally weekly for 12 months will, compared to placebo, result in improved CFR and myocardial tissue perfusion, as assessed by quantitative PET imaging, in stable coronary artery disease patients with diabetes or metabolic syndrome. (2) To test the hypothesis that LDM at a target dose of 15 to 20 mg orally weekly for 12 months will, compared to placebo, result in improved LV myocardial mechanics, as assessed by transthoracic echocardiography, and that this functional improvement will be correlated with the change in CFR after 12 months of treatment. Additional exploratory analyses will assess the relationship of changes in CFR and LV function with quality of life scores, circulating biomarkers of inflammation and cardiac injury, and clinica outcomes. The use of physiologic imaging techniques integrated into clinical care to investigate mechanisms linking inflammation to cardiovascular complications will facilitate needed clinical translation.